This invention relates to the regulation of eucaryotic gene expression by procaryotic proteins.
Commercial production of eucaryotic proteins may involve the in vivo expression of cloned genes. Such cloned genes may be expressed in either procaryotic or eucaryotic systems. Some proteins, for example, Tissue Plasminogen Activator factor, are best synthesized in a eucaryotic cell since the protein must be correctly folded to be functional and for some proteins this process cannot, as yet, be performed by procaryotic cells.
Some cell lines which have cloned genes to produce proteins, for example, those that produce Colony Stimulating Factor, are unstable possibly because the protein produced is deleterious to the cells producing it. In procaryotes such problems are overcome by expressing the cloned gene from a regulated promoter. For example, by altering environmental conditions the promoter can be used to reduce gene expression during cell growth and then to increase expression when required. Although the cells may die when gene expression is turned on, the protein is produced and the cells can be readily replenished. In eucaryotic cells some promoters have been characterized which also regulate gene expression, for example, the promoter of the metallothionine gene of Mouse and the heat shock promoter of Drosophila melanogaster (Sinclair et al., 1985, J. Mol. Cell. Biol. 5:3208).